Sorting of objects based upon size is extremely useful in many technical fields. For example, many assays in biology require determination of the size of molecular-sized entities. Of particular importance is the measurement of length distribution of DNA molecules in a heterogeneous solution. This is commonly done using gel electrophoresis, in which the molecules are separated by their differing mobility in a gel matrix in an applied electric field, and their positions detected by absorption or emission of radiation. The lengths of the DNA molecules are then inferred from their mobility.
While powerful, electrophoretic methods pose disadvantages. For medium to large DNA molecules, resolution, i.e. the minimum length difference at which different molecular lengths may be distinguished, is limited to approximately 10% of the total length. For extremely large DNA molecules, the conventional sorting procedure is not workable. Moreover, gel electrophoresis is a relatively lengthy procedure, and may require on the order of hours or days to perform.
The sorting of cellular-sized entities is also an important task. Conventional flow cell sorters are designed to have a flow chamber with a nozzle and are based on the principle of hydrodynamic focusing with sheath flow. Most conventional cell sorters combine the technology of piezo-electric drop generation and electrostatic deflection to achieve droplet generation and high sorting rates. However, this approach offers some important disadvantages. One disadvantage is that the complexity, size, and expense of the sorting device requires that it be reusable in order to be cost-effective. Reuse can in turn lead to problems with residual materials causing contamination of samples and turbulent fluid flow.
Another disadvantage of conventional sorting technologies is an inability to readily integrate sorting with other activities. For example, due to the mechanical complexity of conventional sorting apparatuses, pre-sorting activities such as labeling and post-sorting activities such as crystallization are typically performed on different devices, requiring physical transfer of the pre- and post-sorted sample to the sampling apparatus.
This transfer requires precise and careful handling in order to prevent any loss of the frequently small volumes of sample involved. Moreover, sample handling for conventional sorter structures is time-consuming. The resulting delay may hinder analysis of materials having limited lifetimes, or prevent sorting that is based upon time-dependent criteria.
Therefore, there is a need in the art for a simple, inexpensive, and easily fabricated integratable sorting device which relies upon the mechanical control of fluid flow rather than upon electrical interaction between the particle and the solute.